Hydrochloric Acid → 6-Iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-benzoimidazol-2-yl}-1H-indazole

HRID 2181530Notes

Reaction equation

HRID 2181530 reaction equation
N[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:19]3[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22]4[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=4[N:20]=3)=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.Cl.[N+]([O-])([O-])=O.[Na+].[I-:42].[K+]>C(O)(=O)C.O.II>[I:42][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:19]3[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:22]4[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=4[N:20]=3)=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 24268Sodium NitrateHCID 229806486-amino-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)ethoxymethyl]-1-H-benzoimidazol-2-yl}-1-H-indazole

Product 1

HCID 218774466-Iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-benzoimidazol-2-yl}-1H-indazoleYield 52%

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent5×

Conditions

Temperature
0 °C

Procedure

A solution of 6-amino-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1-H-benzoimidazol-2-yl}-1-H-indazole (500 mg, 0.98 mmol) in acetic acid (15 mL) was diluted with H2O (1.0 mL) and stirred at 0° C. Concentrated HCl (250 μL, ˜3 mmol) in H2O (250 μL) was added. Sodium nitrate (90 mg, 1.3 mmol) in H2O (300 μL) was added, and the reaction stirred for 8 min. Iodine (10 mg) and a solution of potassium iodide (250 mg, 1.3 mmol) in H2O (250 μL) were added, and the frothing reaction stirred for 30 min at 23° C. The reaction was diluted with H2O (25 mL) and extracted with ethyl acetate (2×20 mL). Organics were washed with saturated sodium metabisulfite solution (10 mL) and brine (10 mL), dried (Na2SO4), and concentrated in vacuo. Purification by silica gel chromatography (8% ethyl acetate/hexanes) gave 316 mg (52%) of 6-iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1-H-benzoimidazol-2-yl}-1-H-indazole as a faintly yellow oil, which slowly crystallized to a white solid. 1H NMR (300 MHz, CDCl3) δ 8.45 (d, 1H, J=9.0 Hz), 8.05 (s, 1H), 7.91-7.88 (m, 1H), 7.67-7.62 (m, 2H), 7.38-7.34 (m, 2H), 6.24 (s, 2H), 5.77 (s, 2H), 3.65-3.57 (m, 4H), 0.93 (t, 2H, J=8.1 Hz), 0.85 (t, 2H, J=8.1 Hz), -0.04 (s, 9H), −0.15 (s, 9H). Anal. (C26H37N4O2Si2) C, H, N. Calculated: C, 50.31; H, 6.01; N, 9.03. Found: C, 50.55; H, 6.08; N, 9.00.

Workup

  1. stirringthe reaction stirred for 8 min
  2. customthe frothing reaction
  3. stirringstirred for 30 min at 23° C
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. washOrganics were washed with saturated sodium metabisulfite solution (10 mL) and brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography (8% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d1cedf119b784c849b86296c5bb4383a
Source dataset
uspto-grants-2005_05
Patent number
US06891044B2

Reaction notes

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